DNA Methyltransferase Inhibitor Hydralazine Induces Upregulation of Somatostatin Type 2 Receptors in Human Neuroendocrine Tumor Cells


Introduction: Epidrugs like DNA methyltransferase inhibitors (DNMTi) can increase somatostatin receptor type 2 (SST2) expression in neuroendocrine tumor (NET) cells in vitro and in vivo. This effect could be used for NET patients with low SST2 expression who are currently ineligible for somatostatin analogue (SSA) treatment. However, the DNMTi known to stimulate SST2 have either a high toxicity profile or are not yet approved.

Aim(s): Evaluation of the antihypertensive and DNMTi drug hydralazine as epidrug for SST2 upregulation.

Materials and methods: Human NET cell lines BON-1 (pancreatic) and GOT-1 (small intestine) were treated with hydralazine alone and in combination with the histone deacetylase inhibitor (HDACi) valproic acid. SST2 expression was determined by RT-qPCR and internalization studies with radiolabelled somatostatin analogue were performed.

Conference: 17th Annual ENETSConcerence (2020)

Presenting Author: Refardt J

Authors: Refardt J, Klomp I, van Koetsveld P, Dogan-Oruç F, de Herder W,

Keywords: somatostatin type 2 receptor, BON-1, GOT-1, upregulation, DNA methyltransferase inhibitor, histone deacetylase inhibitor, epigenetic,

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